Hyperpolarized 129Xe MRI for imaging NK cell therapy of lung metastasis

超极化 129Xe MRI 用于肺转移的 NK 细胞治疗成像

• 批准号: 10646013
• 负责人: James A Bankson
• 金额: $ 18.93万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10646013
• 关键词: Address; Adoptive Transfer; Affect; Allogenic; Anatomy; Animals; Antigens; Biodistribution; Biopsy; Cell Culture Techniques; Cell Therapy; Cells; Cellular immunotherapy; Chemicals; Child; Childhood Cancer Treatment; Clinic; Clinical; Development; Erythrocytes; Excision; FDA approved; Fluorocarbons; Foundations; Gases; Goals; Image; Imaging Device; Immune; Immunotherapy; Infusion procedures; Inhalation; Kinetics; Label; Logistics; Lung; Magnetic Resonance Imaging; Malignant Neoplasms; Metastatic Neoplasm to the Lung; Methods; Modality; Modeling; Monitor; NK cell therapy; Natural Killer Cell Immunotherapy; Natural Killer Cells; Neoplasm Metastasis; Patients; Phase I Clinical Trials; Physiology; Plasma; Positron-Emission Tomography; Protocols documentation; Radiation; Radiation Dose Unit; Recurrence; Refractory; Reporting; Resolution; Respiratory physiology; Safety; Sensitivity and Specificity; Solid Neoplasm; Structure of parenchyma of lung; T-Lymphocyte; Technology; Therapeutic; Time; Tissues; Tracer; Treatment Failure; Validation; Visualization; Water; absorption; amphiphilicity; anatomic imaging; biomedical imaging; cancer therapy; cellular imaging; clinical translation; cost; cytotoxicity; density; detection sensitivity; electronic cigarette use; feasibility testing; imaging approach; imaging biomarker; imaging modality; immune imaging; improved; in vivo; innovation; insight; interest; iron oxide nanoparticle; lung imaging; metabolic imaging; migration; mortality; nanoDroplet; non-invasive imaging; novel strategies; nuclear imaging; osteosarcoma; pediatric patients; respiratory gas; respiratory imaging; response; serial imaging; soft tissue; success; superparamagnetism; translatable strategy; tumor; volunteer

Abstract. Emerging cell-based therapies may greatly improve therapeutic success of cancer treatment. NK cell immunotherapy is particularly important in treatment of pediatric cancers, where information on tumor immunogens is lacking. Recently, there has been increased interest in the use of adoptive transfer of ex-vivo expanded NK cells for the treatment of solid tumors due to their innate features, higher safety compared to T cells and lower cost. This emerging therapy is of particular importance in osteosarcoma where 30-35% of patients die of pulmonary metastases due to a treatment-failure rate of 85% in this patient group. However, an important problem with implementation of cell therapies in the clinic is our inability to readily assess the presence and distribution of therapeutic cells after administration. Visualization of immune cell distribution and migration with non-invasive imaging could offer significant new insight into the progression of immunotherapy between infusion and invasive biopsy or resection. Although there are a number of viable approaches for imaging of immunotherapy, all current strategies have limitations and no technology has been proven as a single solution for longitudinal imaging of cellular immunotherapies. Therefore, it is important to continue pushing the limits of available imaging tools in order to find solutions that would address the pressing clinical needs. Hyperpolarized (HP) 129Xe MRI has recently emerged as a promising modality for direct imaging of respiratory function and gas absorption. Spectral separation between HP 129Xe gas in the airspace, tissue/plasma, and red blood cells permits quantification of gas absorption and exchange. Further, a few exploratory studies have demonstrated that chemical exchange saturation transfer (CEST) of HP 129Xe in perfluorocarbon nanodroplets (PFC NDs) can significantly enhance sensitivity to the presence of PFC ND’s due to a strong chemical shift between 129Xe gas in PFC and water. We see these developments as a tremendous opportunity to develop clinically translatable strategy for imaging NK cell therapy in the lungs. Here we propose to develop foundation for HP 129Xe CEST (hyperCEST) MRI of NK cells in vivo. The secondary goal is identification of imaging biomarkers of functional HP 129Xe MRI that may provide additional insight into response to cell immunotherapy. We will rely on our extensive expertise in (i) synthesis and applications of PFC NDs in biomedical imaging including cell labeling, and (ii) quantitative MRI, multinuclear imaging (13C, 19F, 129Xe) and metabolic imaging. Our hypothesis is that labeling of NK cells with PFC NDs optimized for 129Xe hyperCEST MRI will not adversely affect their functionality and will allow non-invasive NK cell monitoring with high sensitivity and specificity in the lungs. At the completion of these studies we will have a combination of optimized and validated probes for NK cell 129Xe hyperCEST MRI with corresponding imaging protocols that will provide foundation for further development of this promising technology towards clinical translation.

抽象的。新兴的基于细胞的疗法可以大大提高癌症治疗的治疗成功率。NK细胞 免疫疗法在儿科癌症治疗中特别重要， 免疫原缺乏。最近，人们对使用离体细胞的过继转移越来越感兴趣。 扩增的NK细胞用于治疗实体瘤，由于其先天特征，与T细胞相比， 电池和更低的成本。这种新兴疗法在骨肉瘤中特别重要，30-35%的患者 在该患者组中，由于85%的治疗失败率而死于肺转移。然而，一个重要的 在临床中实施细胞疗法的问题是我们不能容易地评估细胞的存在， 给药后治疗细胞的分布。免疫细胞分布和迁移的可视化， 非侵入性成像可以提供重要的新见解，以了解免疫治疗的进展， 和侵入性活检或切除。虽然有许多可行的方法来成像， 免疫疗法，所有目前的策略都有局限性，没有技术已被证明是一个单一的解决方案 用于细胞免疫疗法的纵向成像。因此，重要的是要继续推动极限， 我们将利用现有的成像工具，以找到解决紧迫临床需求的解决方案。超极化 (HP)129 ~（129）Tc MRI最近已成为一种很有前途的方法，用于直接成像呼吸功能和气体 吸收空气空间中的HP 129氦气、组织/血浆和红细胞之间的光谱分离允许 气体吸收和交换的量化。此外，一些探索性研究表明， 在全氟化碳纳米液滴（PFC ND）中HP 129的化学交换饱和转移（CEST）可以 由于129 Ω气体之间的强烈化学位移， 在PFC和水中。我们认为这些发展是一个巨大的机会， 在肺部成像NK细胞治疗的策略。在这里，我们建议为HP 129 CEST开发基础 （hyperCEST）体内NK细胞的MRI。第二个目标是识别功能性肿瘤的成像生物标志物。 HP 129 MRI可以提供对细胞免疫治疗反应的额外见解。我们将依靠 广泛的专业知识，（i）PFC ND在生物医学成像（包括细胞标记）中的合成和应用， 和（ii）定量MRI、多核成像（13 C、19 F、129 F）和代谢成像。我们的假设是 使用针对129 kDa hyperCEST MRI优化的PFC ND标记NK细胞不会对其功能产生不利影响 并且将允许在肺中以高灵敏度和特异性进行非侵入性NK细胞监测。完成时 在这些研究中，我们将有一个优化和验证的NK细胞129 kDa hyperCEST MRI探针的组合 与相应的成像协议，将提供基础，为进一步发展这一有前途的 技术向临床转化。